POS1280 CIRCULATING EXTRACELLULAR VESICLES AS A POTENTIAL BIOMARKER OF INTERSTITIAL LUNG DISEASE AND ITS PROGRESSION IN SYSTEMIC SCLEROSIS –A PROSPECTIVE COHORT STUDY
Authors: J. Colic, I. Pruner, N. Damjanov, J. Antovic, M. Sefik Bukilica, A. Antovic
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Extracellular vesicles (EVs) are membrane-coated vesicles derived from virtually any cell type under different stimuli. Interstitial lung disease (ILD) is the leading cause of death in SSc. So far, only one study demonstrated elevated levels of EVs in patients with SSc-ILD (1), however the association between EVs and progressive ILD (pILD) was not previously investigated. <h3>Objectives</h3> To evaluate the concentration of different subpopulations of EVs in plasma from SSc patients in relation to the occurrence of pILD associated to SSc. <h3>Methods</h3> This was a prospective cohort study, including 59 SSc patients without any comorbidity (31 (52.5%) with ILD and 28 (47.5%) without).The median disease duration in ILD group was 3 years and 6 years in those without. ILD was defined either as X-ray positive findings or ground-glass opacification on HRCT. EVs were analyzed with flow cytometry after staining of platelet-poor plasma with fluorescent cell-specific monoclonal antibodies. The concentration of the following phosphatidylserine-positive EVs was analyzed at baseline: endothelial EVs (EEVs; CD144<sup>+</sup>), platelet EVs (PEVs;CD42b<sup>+</sup>), leucocyte EVs (LEVs; CD45<sup>+</sup>), EVs expressing ICAM1 (CD54<sup>+</sup>), TF (CD142<sup>+</sup>) and HMGB1. The serum concentration of ICAM1,VEGF,and IL6 were measured by ELISA. Lung functional tests were done every 6-12 months over a 3-years period of follow-up (FU). pILD was defined by the decline of forced vital capacity (FVC) from baseline visit of ≥10%, or an FVC decline of 5-9% along with a DLCO decline of &gt;15% [2]. <h3>Results</h3> An inverse relation was noticed in SSc patients between EVs and FVC (EEVs r=-0.3, p&lt;0.05; LEVs r=-0.4, p&lt;0.01; EVsICAM1r=-0.4, p&lt;0.01; EVsTF r=-0.4, p&lt;0.01; EVS HMGB1r=-0.3, p&lt;0.05). Significantly increased levels of VEGF, ICAM1, IL6, PEVs, and EVs expressing ICAM1, TF or HMGB1 were found in SSc ILD cohort compared to those without (p&lt;0.05, respectively). There was a positive association between all explored EVs and VEGF in ILD group (p&lt;0.05). Multivariable (Ml) logistic regression (R)' adjusted for VEGF raveled that PEVs(OR 1.004, 95%CI 1.001-1.01) and EVs ICAM1 (OR 1.3, 95%CI 1.1-1.5) were independently associated with ILD. Over a FU period, 12/31ILD patients developed pILD, of which 58% had early diffuse subtype with &lt; 1-year disease duration and were anti Scl 70 positive. Only 4/12 pILD patients have ever been treated with imunossupresive therapy. pILD occurred within 1st FU year in 50% of patients. All analyzed EVs (Figure 1), IL6 and VEGF, were found elevated in pILD (p&lt;0.05, respectively). Moreover, the levels of PEVs, EVs expressing ICAM1 (AUC 0.9, p&lt;0.001, respectively),TF, HMGB1, EEVs and LEVs (AUC 0.7, p&lt;0.05, respectively) showed good validity in identifying pILD. There was only a positive correlation between VEGF and both EVs ICAM1 (r=0.8, p&lt;0.01) and EVs HMGB1 (r=0.7, p&lt;0.01) within pILD group. Applying Ml Cox R controlling for VEGF, EVs ICAM1 were confirmed independently significantly associated with pILD (OR 1.1, 95% CI 1.02-1.1). <h3>Conclusion</h3> Our results provide evidence that different circulating EV subpopulations might play a role not only in SSc ILD pathogenesis but also in the genesis of pILD. EVs expressing ICAM1 could be a novel predictive biomarker of SSc-related ILD progression, identifying patients who would potentially benefit from early aggressive treatment. <h3>References</h3> [1]D Leleu et al. Elevated Circulatory Levels of Microparticles Are Associated to Lung Fibrosis and Vasculopathy During Systemic Sclerosis. Front Immunol. 2020 Oct 23;11:532177. [2]O Distler et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease.Eur Respir J. 2020 May; 55(5): 1902026. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.